Much of what goes on at the cell surface relates to the recognition by the cell of substances around it. A prime example is the binding of soluble hormones by the cell and its response to such binding. Another important aspect of cell surface recognition is the interaction of the cell with insoluble structures that surround it. Such a structure can be the surface of another cell or the extracellular matrix.
Although the interactions of cells with one another and with extracellular matrices are not well understood, they play an important role in the life of the cell. For example, cell-matrix and cell-cell interactions seem to tell a cell where in the body it is supposed to be or where it is supposed to go if it has to migrate. A particularly intriguing example is nerve cells which send out processes to appropriate positions and thereby form connections to distant parts of the body. Positional signalling is obviously impaired in cancer since tumors invade and disseminate into parts of the body inappropriate for their cell of origin. In fact, as our understanding of the cell-matrix and cell-cell interactions increases and their exploration becomes possible, this field is very likely to develop into a new, important frontier of medicine.
Both proteins and carbohydrates at the cell surface can participate in the cell-matrix and cell-cell interactions. Extracellular matrices are composed of an insoluble meshwork of protein and carbohydrate that is laid down by cells and fills most of the intercellular spaces. Matrices in different locations in the body consist of different combinations of collagens, proteoglycans, elastin, hyaluronic acid and various glycoproteins such as fibronectin and laminin. Virtually all of the extracellular matrix glycoproteins and collagens that have been identified interact with cells.
The most readily observable result of the interaction of cells with the extracellular matrix molecules is cell adhesion. The adhesive properties of the extracellular matrix proteins can be easily demonstrated in vitro by plating cells onto a surface coated with extracellular matrix material or with one of the purified matrix proteins. The cells will rapidly adhere to such a surface and spread on it. However, the adhesive proteins not only promote adhesion, they also stimulate cell migration. When confronted with limiting concentrations of an adhesive protein applied as a gradient on a surface, cells move toward the higher concentration.
More complex ways in which extracellular matrices influence cells are to promote cell differentiation, survival and growth. One of the extracellular matrix proteins, laminin, has particularly striking effects on cells. This protein, which is present in the specialized extracellular matrix sheets, basement membranes, promotes the attachment and migration of cells and plays a role in differentiation and tumor metastasis. Laminin also promotes and guides the growth of nerve cell processes, or neurites.
These interactions between cells and laminin are thought to be mediated by cell surface receptors which function as the adhesion receptor for laminin. The full nature of the receptor, or receptors, that mediate the effects of laminin on cells is still unknown.
There thus exists a need to identify and isolate laminin adhesion receptors. The availability of isolated receptor will allow production of antibodies specific for this receptor, which could be used, for example, to assay for the expression of laminin receptors at the surface of tumor cells. Compounds, such as recombinant protein fragments that bind to the receptor, can be used to reproduce the activity of laminin or to inhibit the adhesion of cells to laminin- containing structures. Moreover, there exists a need to be able to target liposomes to specific tissues for therapeutic or other purposes. The present invention satisfies these needs and provides additional advantages as well.